Huang Yan, Chen Rong, Chen Ye, Lü Xiaoying
State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, 2# Si Pailou, Nanjing, 210096, China.
Sci Rep. 2025 Jul 24;15(1):26923. doi: 10.1038/s41598-025-12477-7.
The aim of this study was to explore the mechanisms in silver nanoparticle (AgNP)-induced cytotoxicity from gene to metabolite levels through an integrative analysis of transcriptomics and metabolomics results. First, transcriptome sequencing technology revealed 1365, 1241, and 2790 genes differentially expressed within human dermal fibroblasts (HDFs) after 4, 8, and 24 h of exposure to silver nanoparticles, which were involved in 250, 248, and 280 biological pathways. Then, by comparing with the metabolomics results, 7 metabolic pathways (purine metabolism pathway, glycerophospholipid metabolism pathway, etc.), with 9 key upstream genes (ADCY4, SPHK1, etc.) and 8 downstream metabolites (xanthine, choline, etc.) jointly involved were found relate to AgNP-induced cytotoxicity. Finally, the results of the validation experiments revealed that AgNPs exerted the toxic effects through these pathways, inducing oxidative stress, affecting energy metabolism, arresting the cell cycle, disrupting the cytoskeleton, inhibiting cell proliferation, and triggering apoptosis.
本研究的目的是通过对转录组学和代谢组学结果的综合分析，从基因到代谢物水平探索银纳米颗粒（AgNP）诱导细胞毒性的机制。首先，转录组测序技术显示，在人皮肤成纤维细胞（HDFs）暴露于银纳米颗粒4、8和24小时后，分别有1365、1241和2790个基因差异表达，这些基因涉及250、248和280条生物学途径。然后，通过与代谢组学结果进行比较，发现7条代谢途径（嘌呤代谢途径、甘油磷脂代谢途径等）、9个关键上游基因（ADCY4、SPHK1等）和8个下游代谢物（黄嘌呤、胆碱等）共同参与了AgNP诱导的细胞毒性。最后，验证实验结果表明，AgNPs通过这些途径发挥毒性作用，诱导氧化应激、影响能量代谢、阻滞细胞周期、破坏细胞骨架、抑制细胞增殖并引发细胞凋亡。
